The major objective of this proposal is to understand the interaction of endogenous virogene and src gene expression with environmental factors in transformation of rat cells. We have established a Sprague-Dawley (SD-1) rat embryo cell model system which is exceptional in that the cells release an ecotropic endogenous type C virus (SD-RaLV) at an early passage level (P13) and undergo transformation about 20-30 passages later. This transformation event is considerably accelerated by treatment with a chemical carcinogen. The SD-RaLV has the unique property of rescuing endogenous src gene nucleotide sequences as novel stable sarcoma viruses (RaSV) in vitro. RaSVs are rescued upon cocultivation of transformed SD cells with several chemically or DNA virus transformed transplant rat tumors into which no sarcoma virus was ever exogenously introduced. These newly derived RaSVs differ from the Harvey and Kirsten strains of sarcoma virus in that they are of purely rat origin. We will compare the biological, biochemical and immunological properties of RaLV spontaneously released from transformed and nontransformed SD cells and other previously described RaLV strains. We will examine the role of in vivo transplantation in activation of endogenous src gene expression. The in vivo pathogenicity of RaLV and RaSV tumor cells will be compared by molecular hybridization one to another and to Harvey and Kirsten sarcoma viruses. An identification of RaSV encoded src protein will be carried out and an effort made to determine their function in the cell transformation process. The physical composition of RaSV and RaLV genomes will be examined by EM, heteroduplex mapping and genome sizing. We will attempt to correlate endogenous RaLV and src gene expression at transcriptional, translational and complete or rescuable virus levels with sequential events leading to chemical or spontaneous transformation of rat cells in vitro and in vivo.